BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Lecture 8: Physical Hydrogels Last Day Overview of biomedical applications of hydrogels Structure of covalent hydrogels Thermodynamics of hydrogel swelling Today Bonding in physical hydrogels Structure and thermodynamics of block copolymer hydrog Reading L.E. Bromberg and E.S. Ron, Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery, Adv. Drug Deliv. Rev., 31, 197(1998) Associative forces in physical hydrogels Cross-link structure in physical hydrogels ·Drⅳ ing associative forces 1. Hydrophobic associations/Van der Waals forces i. LCST polymers, hydrophobic-hydrophilic block copolymers 2. Micellar packing 3. Hydrogen bonding(Rubner) 4. lonic bonding(later lecture) 5. crystallizing segments 6. Combinations of the above interactions o Peptide interactions(e.g. coiled coils)(1) Stability requires cooperative bonding interactions(2)(Guenet, Thermoreversible gelation of polymers and o Individual non-covalent bonds are relatively weak o Strength of covalent bond Hydrophobic association o lonic bond o Hydrogen bond in water o Cooperativity: lowered energy barrier for second and subsequent bonds after first has formed Used in biological associations Lecture 8 sical gels 1of12
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 8 – Physical gels 1 of 12 Lecture 8: Physical Hydrogels Last Day: Overview of biomedical applications of hydrogels Structure of covalent hydrogels Thermodynamics of hydrogel swelling Today: Bonding in physical hydrogels Structure and thermodynamics of block copolymer hydrogels Reading: L.E. Bromberg and E.S. Ron, ‘Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery,’ Adv. Drug Deliv. Rev., 31, 197 (1998) Associative forces in physical hydrogels Cross-link structure in physical hydrogels • Driving associative forces: 1. Hydrophobic associations/ Van der Waals forces i. LCST polymers, hydrophobic-hydrophilic block copolymers 2. Micellar packing 3. Hydrogen bonding (Rubner) 4. Ionic bonding (later lecture) 5. crystallizing segments 6. Combinations of the above interactions o Peptide interactions (e.g. coiled coils)(1) • Stability requires cooperative bonding interactions(2) (Guenet, Thermoreversible gelation of polymers and biopolymers) o Individual non-covalent bonds are relatively weak: o Strength of covalent bond: o Hydrophobic association: o Ionic bond: o Hydrogen bond in water: o o Cooperativity: lowered energy barrier for second and subsequent bonds after first has formed o Used in biological associations
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 · Alpha helix,beta non- cooperative interactions Unstable, no gelation cooperative interactions sheet Stable interactions, gel forms General characteristics of physical gel biomaterials o Dehydration of hydrophobes/hydrophobic association PEO-b-PPo-b-PEO, PPo-b-PEO-b-PPo(commercially known as Pluronics(BASF)) o Similar associative properties from PLGA-PEG-PLGA copolymers and PE PLGA-PEG copolymers 粥 Example blocks: Poly(ethylene glycol)(PEG) CHCH Hydrophilic B blocks Hydrophobic A blocks 。 CoacH R Poly(propylene oxide)(PPO Poly(butylene oxide)(PBO) Lecture 8 sical gels 20f12
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 8 – Physical gels 2 of 12 • Alpha helix, beta sheet non-cooperative interactions: cooperative interactions: Unstable, no gelation Stable interactions, gel forms General characteristics of physical gel biomaterials o Dehydration of hydrophobes/hydrophobic association o Examples: • PEO-b-PPO-b-PEO, PPO-b-PEO-b-PPO (commercially known as Pluronics (BASF)) 2 o Similar associative properties from PLGA-PEG-PLGA copolymers and PEGPLGA-PEG copolymers water Hydrophilic B blocks Hydrophobic A blocks Poly(propylene oxide) (PPO) Poly(butylene oxide) (PBO) Poly(ethylene glycol) (PEG) Example blocks: CH3O CH3 O O O HO-(CH-C-O-CH-C-O-)x-(CH2-C-O-CH2-C-O)y-(CH2-CH2-O)zPLGA CH3O CH3 O O O (CH-C-O-CH-C-O-)x-(CH2-C-O-CH2-C-O)y-H PEG PLGA PEO PPO PEO
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Poly(N-isopropylacrylamide) CHe-CH ordered water molecules minimize water-hydrophobe contacts) Hydroxypropylmethyl cellulose(natural biopolymer) Hydroxypropyl groups dehydrate to associate and form a gel o Micellar packing Pluronics PEO-PPo-PEo block copolymers Cubic lipid gel phases(3) 8小 FIG 1. Schematic model of a bicontinuous cubic phase composed monoolein wate a membrane protein, The matrix consists of Fig.2. Structure of glyceryimonoleate-water cubic phase in three and w conr ydrophobic proteins dillie latelein or mono dimensions with inset showing the lipid bilayer. (Adapted with cating aqueous channel system(see texi modifications from Refs. 14, 39) Sara bu straat 25, 1055 KV Amsterdam, The Ne (Landau and Rosenbusch 1996(4)) Lecture 8 sical gels 3of12
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 8 – Physical gels 3 of 12 • Poly(N-isopropylacrylamide) ordered water molecules (minimize water-hydrophobe contacts) Dehydration allows water to disorder (entropically-driven) ∆S = Sdehydrated - Shydrated > 0 • Hydroxypropylmethyl cellulose (natural biopolymer) o Hydroxypropyl groups dehydrate to associate and form a gel o Micellar packing o Examples: Pluronics PEO-PPO-PEO block copolymers Cubic lipid gel phases(3) (Landau and Rosenbusch 1996(4))
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 micelle 崇 5 mm http://www.ecs.umass.edw/hamilton/matthewlle(micellarcrystalfigurefromwebsiteMatthewBhatia,andRoberts o 5mm hydrogel shown above is a composite box formed by Sciperio printer from Pluronic F-127 and PPF-CO-PEG o Hydrogen bonding o Hydrogen bonds can form between H and C, N, o, and F o Examples Poly (vinyl alcohol) Poly(vinyl alcohol)/PEO blends N一H tcm-H- 一N~o…H-N o Polymers that can form hydrogen bonded gels(5) Poly(vinyl alcohol) Gelatin(natural biopolymer) From Sigma pro o Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular weights, present in collagen. The proteins are extracted by boiling skin, tendons, ligaments, bones, etc in water. Type A used as a stabilizer adhesives, cements, lithographic and printing inks, plastic compounds s thickener and texturizer in foods in the manufacture of rubber substitutes artificial silk, photographic plates and films, matches, and light filters for Lecture 8 sical gels 4of12
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 8 – Physical gels 4 of 12 5 mm PEO PPO PEO (micellar crystal figure from website, Matthew, Bhatia, and Roberts; http://www.ecs.umass.edu/hamilton/matthew_julie.htm) o 5mm hydrogel shown above is a composite box formed by Sciperio printer from Pluronic F-127 and PPF-co-PEG o Hydrogen bonding o Hydrogen bonds can form between H and C, N, O, and F o Examples: Poly(vinyl alcohol) Poly(vinyl alcohol)/PEO blends o Polymers that can form hydrogen bonded gels(5): Poly(vinyl alcohol) Gelatin (natural biopolymer) o From Sigma product sheet: o Gelatin is a heterogeneous mixture of water-soluble proteins of high average molecular weights, present in collagen. The proteins are extracted by boiling skin, tendons, ligaments, bones, etc. in water. Type A used as a stabilizer, thickener and texturizer in foods; in the manufacture of rubber substitutes, adhesives, cements, lithographic and printing inks, plastic compounds, artificial silk, photographic plates and films, matches, and light filters for
BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 mercury lamps; in textiles; to inhibit crystallization in bacteriology and prepare cultures; in PCR hybridization in molecular biology; in the pharmaceutical industry as a suspending agent, encapsulating agent and tablet binder; and in veterinary applications as a plasma expander and o Percec: form hydrogels by H-bonding between water-insoluble short chains and long water-soluble end 4 cowned on moose noea epon lonic bondi o Sodium alginate (7)(Grant, Morris, FEBS Lett. 32, 195 (1973)) Crosslinked by divalent cations, forming salt bridges o Sensitive to salt concentration in physiological locations rosslinked by blending with cationic polymer o E.g. chitosan, polylysine Used extensively for gentle cell encapsulation Lecture 8 sical gels 5of12
BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 8 – Physical gels 5 of 12 mercury lamps; in textiles; to inhibit crystallization in bacteriology and prepare cultures; in PCR hybridization in molecular biology; in the pharmaceutical industry as a suspending agent, encapsulating agent and tablet binder; and in veterinary applications as a plasma expander and hemostatic sponge. o Percec: form hydrogels by H-bonding between water-insoluble short chains and long water-soluble chains (Percec and Bera(6)) o Ionic bonding o Examples: o Sodium alginate(7) (Grant, Morris, FEBS Lett. 32, 195 (1973)) Crosslinked by divalent cations, forming salt bridges o Sensitive to salt concentration in physiological locations Crosslinked by blending with cationic polymer o E.g. chitosan, polylysine Used extensively for gentle cell encapsulation